tbuckley/cabot-search huggingface dataset:
Correction: Porphyromonas Gingivalis Promotes Colorectal Carcinoma by Activating the Hematopoietic NLRP3 Inflammasome
Authors: Xi Wang, Yiqun Jia, Liling Wen, Wenxin Mu, Xianrui Wu, Tao Liu, Xiangqi Liu, Juan Fang, Yizhao Luan, Ping Chen, Jinlong Gao, Ky-Anh Nguyen, Jun Cui, Gucheng Zeng, Ping Lan, Qianming Chen, Bin Cheng, Zhi Wang
Journal: Cancer Research (2022)

In the original version of this article (1), there was an error in Fig. 5C. Specifically, the DAPI image used for the control MC38 tumor tissue immunofluorescence was mistakenly taken from another field and did not match the DAPI staining in the merged image. The correct image has been provided, and the error has been corrected in the latest online HTML and PDF version of the article. The authors regret this error.
Association of PADUA and R.E.N.A.L. scores with cumulative morbidity after partial nephrectomy: A standardized assessment of complications in the context of preoperative nephrometry
Authors: D.K. Filipas, H. Yu, C. Spink, M. Rink, S. Riechardt, P. Gild, P. Marks, M. Fisch, R. Dahlem, C.P. Meyer, M.W. Vetterlein
Journal: European Urology (2022)
Implementing the follow-up schedule after radical nephrouretrectomy for low risk upper tract urothelial carcinoma
Authors: A. Martini, C. Lonati, L. Nocera, G. Fallara, L. Afferi, G. Basile, S. Scuderi, R. Leni, M. De Angelis, P. Karakiewicz, A. Gallina, G. Gandaglia, F. Montorsi, A. Briganti, S. Shahrokh, M. Moschini
Journal: European Urology (2022)
Minimally-invasive partial nephrectomy employing 4K visualization system with OPAL 1 near-Infrared and indocyanine green technology
Authors: P. Diana, A. Gallioli, A. Piana, A. Territo, J. Aumatell, A. Bravo, J.M. Gaya, J. Huguet, A. Rosales, F. Sanguedolce, P. Gavrilov, J. Palou, A. Breda
Journal: European Urology (2022)
Bariatric Surgery and Cancer Risk
Authors: Anita P. Courcoulas
Journal: JAMA (2022)

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Clinical utility of urine tumor DNA in bladder cancer patients.
Authors: Hailong Hu, Yuanjie Niu, HaiTao Wang, Zhaoxia Guo, Huanhuan Liu, Chong Shen, La Da, Gangjian Zhao, Lili Wang, Zhouliang Wu, Zhe Zhang, Shanbo Cao, Feng Lou, Huina Wang
Journal: Journal of Clinical Oncology (2022)

e16560 Background: Concordance between tumor DNA (tDNA) and urine tumor DNA (utDNA) profiles using paired samples was analyzed. Genomic analysis of utDNA and tDNA showed a high consistency, indicating that urine is an optional sample for noninvasive detection and response evaluation of bladder cancer (BC). Methods: Methods and results data were analyzed from an ongoing study, collecting all cases from Second Hospital Affiliated to Tianjin Medical University. Cases with pathologically confirmed BC and matching tissue/urine/whole blood before treatments were recruited. In 85 patients, 48 with paired samples were enrolled in this analysis after excluding 37 paired samples failed in sample QC or sample collection. WES (Whole Exome Sequence) was applied to tDNA and paired white blood cell (WBC) DNA. An Acornmed 808-Gene panel was applied to utDNA and paired WBC DNA. Somatic events, including SNV (single nucleotide variant), InDel (insertion and deletion) of hot genes were analyzed. Consistency of tDNA and utDNA were identified and analyzed in the intersection set between the two chips, and tDNA profiling was used as the“golden standard”. Results: Among 48 patients, 24(50.0%) were MIBC, 21(43.8%) were NMIBC and 41 (81.5%) were male. With neoadjuvant therapy, 23(47.9%) are identified as responders (CR or PR), 7(14.6%) identified as non-responders (SD or PD), 18(37.5%) are still following up. Overall, 75.4% (214/284) tDNA mutations were found in utDNA, and 75.1% (214/285) utDNA mutations were found in tDNA. The top20 genes’ mutation landscape of utDNA highly resembled that of tDNA. The top20 genes could cover 97.9% (47/48) tissue samples and 89.6% (43/48) urine samples. Also, top20 mutated genes showed a strong correlation between tDNA and utDNA(r = 0.7371, p = 0.0002). TP53, KMT2D, ARIDA1A, CREBBP, ERBB2, ERCC2 and KDM6A are the most frequent abnormalities captured in tDNA and utDNA. Interestingly, we also found that the consistency of top20 genes in responders (n = 23, r = 0.7015, p = 0.0006) are higher than non-responders (n = 7, r = 0.4118, p = 0.1853). As a consequence, 70.1% (157/224), 61.8% (21/34) tDNA mutations were found in utDNA, and 72.0% (157/218), 25.0% (21/84) utDNA mutations were found in tDNA in responders and in non-responders, respectively. Conclusions: In brief, utDNA was robustly consistent and highly associated with tDNA, with 61.8%̃75.4% tDNA variations detected in utDNA target sequecing by acornmed 808 panel. The consistency would be higher if TERT promoter included in WES panel. While in non-responders, only 25.0% utDNA mutations were found in tDNA, indicating a spatial and temporal tumor heterogeneity. Our data provided initial prospective evidence on further developing urine as an optional sample for noninvasive detection and response evaluation of BC. The large prospective cohort study is still ongoing.
Dynamic changes in serum analyte levels associated with clinical outcome in squamous cell lung cancer trial SWOG Lung-MAP S1400I of nivolumab ± ipilimumab.
Authors: Edgar Gonzalez-Kozlova, Hsin-Hui Huang, Mary Weber Redman, Roy S. Herbst, Scott N. Gettinger, Lyudmila Bazhenova, Hui Xie, Manishkumar Patel, Kai Nie, Jocelyn Harris, Kimberly Argueta, Ethan Cerami, Joyce Hong, Roshni Biswas, Stephen Van Nostrand, Karen Kelly, Radim Moravec, Diane Del Valle, Seunghee Kim-Schulze, Sacha Gnjatic
Journal: Journal of Clinical Oncology (2022)

9044 Background: While Immune checkpoint blockade (ICB) is standard treatment for lung cancer there are limited biomarkers that predict benefit, pharmacokinetic on-treatment activity or explain progression. S1400I was a randomized Phase III trial of nivolumab(N)+ipilimumab(I) versus N (NCT02154490, PMID 34264316) for ICB naïve, previously treated stage IV or recurrent squamous cell lung cancer. We performed circulating serum protein analysis of serial blood specimens from patients enrolled in S1400I to evaluate if serum proteins levels changed over time, changes differed by treatment arm, and if they were associated with overall survival. Methods: 561 serial blood specimens (baseline, weeks (wk) 3, 7, 9, and progression [PD]) from 160 of 252 eligible patients enrolled to S1400I were analyzed for 92 immuno-oncology analytes with the Olink proximity extension assay. Protein levels were normalized with use of internal controls and quantified as log2 protein expression (denoted as NPX). Linear mixed models evaluated change in expression from baseline at each time point (wks 3,7,9 and PD), and NPX differences at baseline, wk3, and PD depending on best objective response. A Cox model was used to evaluate the association between baseline NPX and survival. Overall survival and longitudinal cytokine expression were jointly modeled using a linear mixed model to estimate dynamic biomarker changes in NPX and a Cox model for survival. The joint models for time-varying NPX values included a random intercept and modeled time using a natural spline with three knots. Significance was defined as P &lt; 0.05. Results: Serum proteins PCDC1, CXCL9, and CXCL10 were increased from baseline at wks 3,7,9 and at PD. CCL19 was increased at wks 3 and 7 but not at wk 9 and PD. IL10 and IFNγ were increased at wk 3 but subsequently returned to baseline. Change in CXCL13 from baseline to PD was larger for N+I versus N. Baseline CCL23, CSF-1, IL6, and MUC-16 were associated with shorter survival (HR &gt; 1). Joint modeling of survival with cytokines showed an increased risk of death (HR &gt; 1) with higher longitudinal serum levels of CXCL13, MMP12, CSF-1, and IL8. Patients achieving objective response had higher IL4 and LAMP3 and lower IL6 and IL8 at baseline and wk 3 compared to non-responders. Conclusions: Measurements of blood circulating soluble proteins represent easily accessible biomarkers that may be useful as indicators of outcome, and that will need to be prospectively confirmed. Clinical trial information: NCT02154490.
Implementing systematized patient-facing Lynch syndrome (LS) risk assessment in oncology using the electronic health record (EHR) system.
Authors: Chinedu Ukaegbu, Matthew B. Yurgelun, Alyson Caruso, Leanne McAuliffe, Anu B. Chittenden, Sarah Whittaker, Jessica Cleveland, Brittany Black, Sunyi Zhang, Michael J. Hassett, Nadine Jackson McCleary, Sapna Syngal
Journal: Journal of Clinical Oncology (2022)

10503 Background: Lynch syndrome (LS) is the most common inherited cause of colorectal (CRC) and endometrial cancers. Significant provider and institutional level barriers limit LS detection, even in oncology patients with LS-associated cancers. PREMM5 is a validated tool based on personal and family cancer history that is recommended by national professional societies for LS risk assessment. This project’s goal was to study the feasibility of patient-facing LS risk assessment using a PREMM5 screener embedded in an electronic health record (EHR) system, as a means of improving LS identification. Methods: The PREMM5 LS screener intake questions were adapted to be completed by patients rather than healthcare providers. Screener adaptation and implementation involved iterative review by multidisciplinary experts and multilevel stakeholder engagement. The patient-facing PREMM5 LS screener was embedded in the EHR (Epic) at the Dana-Farber Cancer Institute (DFCI) to enable remote (via the EHR patient portal) and on-site completion (in clinic waiting rooms). All new gastrointestinal (GI) cancer patients seen at DFCI for initial oncology consultation from 6/2020-12/2021 were invited through the portal to complete the screener. PREMM5 scores ≥2.5% were considered “positive”, with genetics referral recommended. Beginning 2/2021, the EHR generated an automated provider-facing alert for positive screens. Results: 35% (1504/4262) of new GI cancer patients completed the screener. 367/1504 (24%) had a positive PREMM5 screen (mean age 53 years), of whom 66% were male, and 62%, 12% and 10% had CRC, neuroendocrine and pancreas cancer respectively. 97% (357/367) of screen positives completed the PREMM5 screener remotely through the portal. 102/367 (28%) received a genetics referral as a result of their positive PREMM5 screen (not including 75 genetics referrals outside this workflow), 13 of whom had a pathogenic variant (PV) on germline testing, including 4 with LS ( MSH2, MSH6, PMS2), and others with PVs in ATM, BRCA2, CHEK2, NTHL1, RAD50 and RECQL4. Conclusions: A practice-wide patient-facing EHR-integrated PREMM5 risk assessment workflow is feasible and identified nearly 1 in 4 general GI oncology patients as warranting genetic evaluation, resulting in the identification of numerous actionable germline PVs. This method of deployment could make genetic risk assessment more accessible to non-genetics providers. The suboptimal screener completion rate and 28% genetics referral rate among positive screens suggest the need for additional refinements, including patient and provider engagement and outreach to positive screens who do not follow up with appointments for genetic evaluation.
The atherosclerotic cardiovascular disease risk score is a reliable tool to identify patients with arteriogenic erectile dysfunction at dynamic penile color doppler duplex ultrasound: Findings from a real-life cross-sectional study
Authors: E. Pozzi, M. Raffo, P. Capogrosso, G. Fallara, F. Belladelli, C. Corsini, D. Cignoli, L. Candela, N. Schifano, A. D'Arma, L. Boeri, E. Ventimiglia, R. Matloob, V. Mirone, F. Montorsi, A. Salonia
Journal: European Urology (2022)
Neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR) and lymphocytes counts as a possible prognostic factor in neuroendocrine tumors of the gastrointestinal tract.
Authors: Alexandra Androsova, Rashida Orlova, Anastasia Ivanova, Natalia P. Beliak, Svetlana Kutukova
Journal: Journal of Clinical Oncology (2022)

e16207 Background: The aim of our study was to investigate the prognostic role of the neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) in PFS and OS of patients with neuroendocrine tumors (NETs) of the gastrointestinal tract. Methods: We analyzed medical records of 69 patients with stage I - IVB NETs of the gastrointestinal tract (25 men, 44 women; median age is 57 years [44.75-66.00]). All patients were treated according to the standard protocols from 2015 till 2020. We examined demographics, clinical stage, tumor morphology, and baseline levels of leukocytes, neutrophils, lymphocytes, monocytes, and PLT. We also analyzed the calculated value of NLR, dNLR, PLR and LMR. Results: The ROC analysis made it possible to determine that the factors, that have a significant impact on the PFS indicator are: absolute (cut-off: ≤2.26; p = 0.0274) and relative (cut-off: ≤30; p = 0.0158) lymphocyte count, NLR (cut-off: 1.85; p = 0.0230) and dNLR (cut-off: 1.40; p = 0.0209). The median PFS of patients whose baseline absolute lymphocyte count 2.26x109/l or less was 34.0 months and was significantly (61%) less than the median PFS in the group of patients with an absolute lymphocyte count greater than cut-off value (p = 0.0122; HR = 0.39: 95% CI 0.19-0.81). The median PFS of patients with relative lymphocyte count £30% was 25.0 months and was significantly (61%) less than the median PFS in the group of patients with lymphocyte count &gt; 30% (p = 0.0082; HR = 0.39: 95% CI 0.20-0.79). The median PFS of patients with NLR &gt; 1.85 was 26.0 months and was significantly (60%) less than the median PFS in the group of patients with NLR1≤.85 (p = 0.0095; HR = 0.40: 95% CI 0.21-0.80). The median PFS of patients with dNLR &gt; 1.40 was 20.0 months and was significantly (60%) less than the median PFS in the group of patients with dNLR≤140 (p = 0.0120; HR = 0.40: 95% CI 0.20-0.82). In multivariant analyses, which contained all significance factors by univariate analysis, count of lymphocytes: lymphocytes≤30% significantly increased the risk of disease progression: p = 0.0344; HR = 0.97; 95% CI 0.94-0.99. Conclusions: Systemic inflammatory markers have demonstrated their diagnostic and predictive value in patients with neuroendocrine tumors of the gastrointestinal tract.
Irreversible electroporation treatment using [18F] PSMA-PET CT in localized prostate cancer: Preliminary study
Authors: D. Shin, C.E. Yoon, H.J. Kwon, H.W. Moon, Y.H. Park, W.J. Bae, H.J. Cho, U-S. Ha, S-H. Hong, S.W. Kim, J.Y. Lee
Journal: European Urology (2022)
Medications mostly associated with urinary retention: Assessment of the Eudravigilance (EV) and the Food and Drug Administration (FDA) Pharmacovigilance database entries
Authors: A. Franco, A. Nacchia, G. Disabato, O.A. Voglino, V. Baldassarri, R. Lombardo, S. D'Annunzio, A. Cicione, L. Rovesti, E. Mancini, G. Guarnotta, A. Guercio, G. Gallo, B. Turchi, C. Gravina, J. Stira, A. Tubaro, C. De Nunzio
Journal: European Urology (2022)
Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease
Authors: Won Sohn, Danbee Kang, Minwoong Kang, Eliseo Guallar, Juhee Cho, Yong-Han Paik
Journal: Clinical and Molecular Hepatology (2022)

This study aimed to investigate the effect of hepatocellular carcinoma (HCC) surveillance using the Korea National Liver Cancer Screening Program on the receipt of curative treatment for HCC and mortality in patients with chronic liver disease.This population-based cohort study from the Korean National Health Insurance Service included 2003 to 2015 claims data collected from 1,209,825 patients aged ≥40 years with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Patients were divided according to HCC surveillance using ultrasonography and serum alpha-fetoprotein every 6-12 months. The study outcomes were the receipt of curative treatment (surgical resection, radiofrequency ablation, or liver transplantation) and all-cause mortality.The study population consisted of 1,209,825 patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (median age, 52.0 years; interquartile range, 46-55 years; 683,902 men [56.5%]). The proportion of participants who underwent HCC surveillance was 52.7% (n=657,889). During 10,522,940 person-years of follow-up, 74,433 HCC cases developed, including 36,006 patients who underwent curative treatment. The surveillance group had a significantly higher proportion of curative treatment for HCC than the non-surveillance group after adjusting for confounding factors (adjusted hazard ratio [HR], 5.64; 95% confidence interval [CI], 5.48-5.81). The surveillance group had a significantly lower mortality rate than the non-surveillance group (adjusted HR, 0.56; 95% CI, 0.55-0.56).HCC surveillance using the national screening program in patients with chronic viral hepatitis or liver cirrhosis provides better opportunity for curative treatment for HCC and improves overall survival.
A phase 2 expanded access study of zanubrutinib (ZANU) in patients (pts) with Waldenström Macroglobulinemia (WM).
Authors: Jorge J. Castillo, Ed Kingsley, Mohit Narang, Habte Aragaw Yimer, Constantin A Dasanu, Jason M. Melear, Morton Coleman, Charles Michael Farber, Mukul Gupta, Jonah Shulman, Emily H. Mantovani, Xiaowei Zhang, Aileen Cohen, Jane Huang
Journal: Journal of Clinical Oncology (2022)

e19522 Background: Bruton tyrosine kinase (BTK) inhibition is an emerging standard of care for WM. The next-generation BTK inhibitor ZANU (BGB-3111), designed to maximize BTK occupancy and minimize off-target inhibition of other kinases, is approved by the United States (US) Food and Drug Administration, Health Canada, and the European Union at a dose of 320 mg once daily (QD) or 160 mg twice daily (BID) for adult pts with WM. BGB-3111-216 is a single-arm expanded access study of ZANU in treatment-naïve (TN) pts who were unsuitable for standard chemoimmunotherapy or pts with relapsed refractory (R/R) WM. This study provides real-world experience with ZANU in pts with WM. Methods: Eligible pts with TN or R/R WM received ZANU 320 mg QD or 160 mg BID orally. Primary endpoint was the number of pts enrolled/treated and enrolling sites. Secondary endpoints included treatment-emergent adverse events (TEAEs) of special interest, disease response rate, progression-free survival (PFS), and overall survival (OS). Response was evaluated by investigator assessment according to the 6th International Workshop on WM ( Br J Haematol. 2013;160(2):171-6) every 6 mo at minimum. The study was closed by the sponsor in July 2021 and active pts were transitioned to commercial ZANU via a patient assistance program. Results: Fifty pts with WM (17, TN; 33, R/R) were enrolled between December 2019 and June 2021 across 10 academic and community medical centers in the US. Median age was 72 years, 54% had intermediate-, 40% had high-risk disease, and the median number of prior therapies for R/R pts was 2. Median treatment exposure was 9.2 mo (range, 1.4-20.0). Thirty-eight (76%) pts had ≥1 TEAE, and 36 (72%) had ≥1 TEAE of special interest. Grade ≥3 TEAEs of special interest were hypertension (8%), infection (8%), atrial fibrillation/flutter (2%), neutropenia (2%), and second primary malignancy (2%). No new safety signals were observed. In pts with ≥1 response evaluation, 39% achieved a best overall response (BOR) of very good partial response. Overall response rate was 85.4% and major response rate was 73.2% (Table). Of the 4 pts with BOR of progressive disease, 3 had IgM values that met partial response criteria before the 6-mo response assessment. PFS and OS were immature due to short follow-up, and the median was not met. Conclusions: These real-world expanded access study results were consistent with the established ZANU profile in WM or other B-cell malignancies when administered as oral monotherapy at 160 mg BID or 320 mg QD in pts with intermediate or high-risk R/R or TN WM. Clinical trial information: NCT04052854. [Table: see text]
Dissecting transcriptional heterogeneity in multiple primary lung cancer by single cell RNA sequencing.
Authors: Wei Guo, Fengwei Tan, Qi Xue, Shugeng Gao, Jie He
Journal: Journal of Clinical Oncology (2022)

e20516 Background: The progression of multiple primary lung cancer has been involved in complex cell changes in composition and metabolic function. However, the role of immune related cells proliferation and epithelial cells differentiation during the synchronous multiple primary lung cancer development is still understudied. Methods: In this study, we performed scRNA sequencing of 167,397 cells from six patients with multiple primary lung cancer, combined with bulk RNAseq and whole exome sequencing. Results: We firstly revealed that both naïve and memory T cells participated in the differentiation of CD8+ T cells. One end state of CD8+ T cells is exhausted T cells and they response to stimulus and positive regulated the cell death. The Other end state is cytotoxic T cells which mainly implicated in regulation of cytokine production included positive regulation of myeloid leukocyte cytokine production involved in immune response, immune effector process, macrophage cytokine production and positive regulation of cytokine production involved in immune response. Multiple functional Treg cells and naïve T cells contributed to the CD4+ T cells origin. In addition, B cells with two main kinds of function also plays an important role in immune response. One is that the regulation and activation of innate immune response have been highly activated. The other were enriched in pathways that antigen binding, processing and presentation including MHC class II Antigen Presentation. We also revealed the cellular metabolic functions during the tumor invasion. The positive regulation of blood vessel diameter has been observed in endothelial cells, while angiogenesis has not been found in early glandular neoplasia of the lung. The development of epithelial cells mainly consists of two function states. One is that some cells response to the stress from immune, and the other is that some will die programmatically and begin to cell circle due to selective pressure with the development of tumor in multiple primary lung cancer. Conclusions: Our study showed a complete landscape of different dynamic cellular changes which might pinpoint the key cellular mechanisms of synchronous multiple primary lung cancer and therefore provided new clues for pathogenesis of tumors.